A pediatric occurrence of crescentic glomerulonephritis associated with antineutrophil cytoplasmic antibodies and mesangial IgA deposits

Antineutrophil cytoplasmic antibody-(ANCA) associated glomerulonephritis usually shows histopathologic features of pauciimmune crescentic glomerulonephritis and occurs late in life. We report a 14-year-old Japanese girl presenting with proteinuria, hematuria and mildly elevated serum creatinine. A renal biopsy specimen demonstrated crescentic glomerulonephritis, immunofluorescence showed mesangial IgA staining. Electron microscopic examination disclosed paramesangial deposits. Serum ANCA against myeloperoxidase (MPO) were detected at high titers. Myeloperoxidase-ANCA-related nephritis accompanied by IgA nephropathy is considered rare in childhood and teen years. Yet, if ANCA assays and detailed electron microscopic examination of renal specimens were performed routinely in patients with rapidly progressive glomerulonephritis, the diagnosis might be more frequent in young patients.     

Cryptococcosis associated with crescentic glomerulonephritis

Crescentic glomerulonephritis (CGN) is an uncommon form of renal injury in childhood. Whereas many infectious processes are known to be linked to CGN, fungal infections typically are not. This report describes an 11-year-old girl who presented with CGN, cutaneous anergy, and cryptococcal mediastinitis. Whereas cryptococcal disease in children is usually associated with immunodeficiency (inherited or acquired), extensive immunologic evaluation of the patient was notable only for relative CD4 lymphopenia with normal CD4/CD8 ratios. Testing for human immunodeficiency virus was negative. Clinical and diagnostic studies are presented, along with a review of the literature regarding glomerular disease and cryptococcal infections.     

ANCA-associated crescentic IgA glomerulonephritis in pregnancy

Only a few reports have documented the presence of crescentic IgA nephropathy associated with antineutrophil cytoplasmic antibodies (ANCA), suggesting an overlap that has therapeutic significance as regards the patients' response to treatment. We report a case of rapidly progressive glomerulonephritis with P-ANCA, with biopsyproven crescentic IgA glomerulonephritis in an 11-week pregnant woman who responded very well to cyclophosphamide and prednisone. Her 24-h urine protein dropped from 5400 mg/day to 516 mg/day and serum creatinine from 2.7 mg/dL to 1.4 mg/dL. To the best of our knowledge, this is the first such case reported in pregnancy. Eighteen months after her initial presentation, she has no significant clinical problems and her laboratory work-up shows stable results.     

Paraneoplastic polymyositis associated with crescentic glomerulonephritis

A female concurrently developed polymyositis (PM), lung cancer, and nephrotic range proteinuria. Renal biopsy revealed crescentic glomerulonephritis. Pathology of lung cancer was proved to be adenocarcinoma. After surgical treatment of lung cancer, the symptoms of PM-associated crescentic glomerulonephritis disappeared. PM is associated with a higher risk of malignancy, though renal involvement in patients with PM is thought to be uncommon. In patients with PM, there have been few reports concerning the coexistence of glomerular disease, including crescent glomerulonephritis. Herein we report a case of crescentic glomerulonephritis-associated PM that was successfully treated after the surgical removal of lung cancer. We consider that such association of PM and crescent glomerulonephritis is rare in adults. Careful evaluation of underlying malignancy is important. The definite treatment is adequate management of underlying malignancy.     

Enterococcal endocarditis associated with crescentic glomerulonephritis

Glomerulonephritis secondary to infective endocarditis (IE) is an uncommon diagnosis and is usually associated with cardiac valvular infection by blood-culture-positive bacteria. We report a case of necrotizing glomerulonephritis associated with culture-positive endocarditis caused by Enterococcus faecalis. The patient presented with renal abnormalities and was further investigated by renal biopsy. He had immune complex-mediated necrotizing and crescentic glomerulonephritis with mesengial and capillary deposition of immunoglobulin M (Ig M), Ig G, and complement 3 (C3). He was treated with antibiotics, including ampicillin and gentamicin. In addition, steroid and cyclophosphamide were administered. The patient died of renal failure 48 days after hospital admission. In conclusion, glomerulonephritis caused by Enterococcus faecalis endocarditis is an immune-complex-mediated disease characterized by necrotizing and crescentic glomerular lesions that can be fatal despite aggressive antimicrobial and immunosuppressive therapy.     

ANCA-positive crescentic glomerulonephritis associated with minocycline therapy

Minocycline is an oral antibiotic widely used for the long-term treatment of acne and rheumatoid arthritis. A few patients develop antineutrophil cytoplasmic antibodies (ANCAs) during minocycline therapy. In this report, the authors describe a case of severe pauci-immune crescentic and necrotizing glomerulonephritis associated with positive cytoplasmic ANCA (C-ANCA) titers and proteinase 3 (PR3) levels after minocycline therapy. Discontinuation of minocycline and initiation of immunosuppressive treatment resulted in improvement of renal function and decline in C-ANCA titers and PR3 levels. A high degree of suspicion, testing for ANCA titers, prompt discontinuation of the drug, and initiation of immunosuppressive treatment are crucial to the diagnosis and treatment of drug-induced ANCA-associated glomerulonephritis.     

Classic and perinuclear anti-neutrophil cytoplasm antibodies and antimyeloperoxidase antibodies in rapidly progressive glomerulonephritis.

Classic anti-neutrophil cytoplasm antibodies (cANCA), perinuclear ANCA (pANCA) and antibodies directed against myeloperoxidase (MPO-Ab) were evaluated in 25 patients with either idiopathic or secondary rapidly progressive glomerulonephritis (RPGN). While cANCA were found almost exclusively in Wegener's granulomatosis, pANCA were detectable in several disorders, including microscopic polyarteritis (mPA), but also idiopathic RPGN. MPO-Ab were frequently found in sera from patients with all types of idiopathic but not of secondary RPGN. These results support the hypothesis that some cases of RPGN are early or limited forms of systematic vasculitis. We then looked for the presence of IgA-ANCA in Henoch-Schoenlein purpura (HSP): we found IgA-ANCA with immunoenzymatic assay but not with immunofluorescence in HSP, in primary IgA-GN and in membranous GN as well, thus suggesting the poor specificity of this type of ANCA. The possible pathologic implications of ANCA were examined in vitro. Serum samples from several patients with ANCA were assessed for their capacity to enhance chemiluminescence generation from resting or PMA-stimulated macrophages. Sera from RPGN and mPA patients displaying anti-MPO activity induced granulocytes to enhance the production of oxygen free radicals, thus suggesting a phlogistic effect of MPO-Ab positive sera.     

Hemorrhagic complications associated with PR3-ANCA crescentic glomerulonephritis

Abstract

Hemorrhagic complications of anti-neutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis are life-threatening conditions. Of these, alveolar hemorrhage is the most common and well-described hemorrhagic complication and is a prominent component of the pulmonary-renal syndrome. The clinical presentation of alveolar hemorrhage is highly variable ranging from mild to serious disease that may require respiratory support. Less attention has been directed at hemorrhagic complications that have been reported in other organs and which may be as severe or more severe with regard to morbidity and mortality. For example, among the most serious non-pulmonary complications are those related to cerebral and gastrointestinal hemorrhage. Cerebral hemorrhage is the clearly the most critical issue with a persistent high mortality rate. The prognosis of gastrointestinal hemorrhage, once an ominous complication has improved with medical and surgical intervention. Not to be dismissed are the consequences of hemorrhagic issues related to skin, soft tissue or muscle involvement. Muscle hematomas, while rare, also accompanied by significant morbidity.     

Anti-endothelial cell antibodies in antineutrophil cytoplasmic antibodies negative pauci-immune crescentic glomerulonephritis

Aim: Pauci‐immune crescentic glomerulonephritis (CrGN) is frequently associated with circulating anti‐neutrophil cytoplasmic antibodies (ANCA). However, in patients with ANCA‐negative pauci‐immune CrGN, the pathogenesis is not clear. Anti‐endothelial cell antibodies (AECA) have been implicated in the pathogenesis of vasculitis. The purpose of this study is to investigate the prevalence of AECA and their possible clinical significance in ANCA‐negative pauci‐immune CrGN. Methods: Sera from 19 patients with ANCA‐negative pauci‐immune CrGN, 26 patients with ANCA‐positive pauci‐immune CrGN and 10 healthy blood donors were collected. Soluble proteins extracted from cultured human umbilical vein endothelial cells were used as antigens and western blot analysis was carried out to detect AECA. Results: In ANCA‐negative pauci‐immune CrGN, 10 of 19 patients were serum IgG‐AECA positive and seven bands reactive with endothelial antigens could be blotted. The prevalence of skin rash and thrombocytosis was significantly higher in patients with anti‐76 kDa and anti‐123 kDa autoantibodies than in patients without, respectively. Birmingham Vasculitis Activity Scores of patients with anti‐200 kDa AECA were significantly higher than in patients without. In the sera of 26 ANCA‐positive cases, 23 were AECA positive and 11 bands could be recognized. The prevalence of total AECA and anti‐90 kDa AECA was significantly lower in patients with ANCA‐negative pauci‐immune CrGN than in patients with ANCA‐positive pauci‐immune CrGN. Conclusion: Anti‐endothelial cell antibodies could be found in sera of patients with ANCA‐negative pauci‐immune CrGN; some AECA might have some clinical significance. The discrepancies of AECA might be a possible contributor to the differences between ANCA‐negative and ANCA‐positive pauci‐immune CrGN.     

Report on intensive treatment of extracapillary glomerulonephritis with focus on crescentic IgA nephropathy

PURPOSE AND DESIGN OF STUDY.: In this retrospective analysis the effects of combined treatmentwith steroid pulses, cyclophosphamide and plasma exchange onsix crescentic IgA glomerulonephritis (IgAGN) patients, selectedon a histological basis, were examined. The histological criteriaincluded involvement of more than 40% of glomeruli by cellularcrescents. The effects of this treatment were compared to thoseobserved in three untreated crescentic IgAGN patients and 12treated patients who had extracapillary glomerulonephritis ofdifferent origins, i.e. ANCA-associated systemic or renal-limitedvasculitis. All patients, except the three crescentic untreatedIgAGN patients, received the same 2-month treatment accordingto a standardized protocol: steroid boli 15 mg/kg methylprednisolonefor 3 consecutive days by intravenous infusion, followed byprednisone per os (1 mg/kg/day for 4 weeks, 0.75 mg/kg/day for4 more weeks), cyclophosphamide per os 2.5 mg/kg/day for 8 weeks,and plasma exchange. RESULTS.: After this 2-month course of therapy, substantial clinical improvementwas observed in both IgAGN and vasculitis patients. However,a second biopsy revealed that florid crescents persisted inIgAGN patients and, unlike the vasculitis group, during thelong-term the initial clinical amelioration disappeared in one-halfof the treated IgAGN cases. Nevertheless, even in the progressivecases, intensive treatment seemed to substantially delay theonset of dialysis. CONCLUSIONS.: Despite some clinical benefits of therapy, short-term reversalof active crescents appears less likely to occur in crescenticIgAGN than in vasculitis-associated crescentic GN. Intensivetreatment seems sufficient to arrest, but inadequate to reverse,phlogistic lesions in IgAGN before development of chronic changes.     

Waldenstr?m's macroglobulinemia associated with amyloidosis and crescentic glomerulonephritis

An unusual case of Waldenstr?m's macroglobulinemia associated with amyloidosis and crescentic glomerulonephritis is described. At autopsy, crescent formation was present in 80% of the glomeruli, and the breaks in the glomerular basement membranes were found at the same place as the deposition of amyloid.     

IgA glomerulonephritis associated with microscopic polyangiitis or Churg-Strauss syndrome.

When renal insufficiency occurs in classical antineutrophil cytoplasm antibody- (ANCA) associated vasculitides, histological examination usually finds pauci-immune focal segmental glomerulonephritis. We report on 2 cases of histologically proven necrotizing vasculitis associated with IgA nephropathy. Concomitant vasculitis and IgA nephropathy has only rarely been reported but this joint occurrence may not be coincidental as its pathophysiology is not known. Among vasculitides, IgA nephropathy has more frequently been associated with Henoch-Schoenlein purpura: one microscopic polyangiitis unusual because the patient simultaneously presented ANCA and microaneurysms, and the other Churg-Strauss syndrome associated with mild renal insufficiency. This uncommon association might represent a possible overlap syndrome between these ANCA-associated vasculitides and IgA nephropathy or simply a new type of glomerulonephritis that must be taken into account in these vasculitides.     

New insight on crescentic glomerulonephritis.

Sir, Diseases involving the renal glomeruli are encountered frequentlyin clinical practice and are the most common cause of end-stagerenal disease worldwide. Crescentic glomerulonephritis and itsclinical corollary, rapidly progressive glomerulonephritis (RPGN),is a potentially fatal disease and one of the few diagnosticemergencies that occur in nephrology in which affected individualslose kidney function     

Transformation of membranous glomerulonephritis into crescentic glomerulonephritis with glomerular basement membrane antibodies. Serial determinations of anti-GBM before the transformation

This case report describes a patient who initially had a pleuritis and arthalgias. During the follow-up he developed first a membranous glomerulonephritis with nephrotic syndrome and subsequently a crescentic, rapidly progressive glomerulonephritis with glomerular basement membrane antibodies (anti-GBM). An analysis of the serum samples obtained during the follow-up revealed no infections at the onset of renal failure. However, anti-GBM could be demonstrated in the serum samples obtained 2 months before the deterioration of the renal function. The anti-GBM did not react with alveolar BM and the patient had no signs of pulmonary hemorrhage. The etiology and the sequence of the pathological events of rapidly progressive glomerulonephritis is discussed in the light of these observations.     

Antineutrophil cytoplasmic antibodies (ANCA) in Chinese patients with anti-GBM crescentic glomerulonephritis

OBJECTIVE: To study the prevalence of ANCA and their target antigen in Chinese patients with anti-GBM crescentic glomerulonephritis (CGN), and to evaluate the possible role of ANCA in Chinese anti-GBM CGN patients with coexisting serum ANCA by studying clinicopathologic features of this disease. MATERIAL AND METHODS: Twenty-three sera were collected from 23 renal biopsy-proven anti-GBM CGN patients. According to the standardized procedures, all of the sera were determined by both, indirect immunofluorescence (IIF) ANCA, and enzyme-linked immunosorbent assay (ELISA) MPO-ANCA, PR3-ANCA and BPI-ANCA. The patients were divided into two groups according to serum ANCA positivity (Group A) or negativity (Group B). Thirty-three ANCA-associated pauci-immune CGN patients were regarded as control group (Group C). Their clinicopathologic features were compared to reveal whether ANCA correlated with disease activity. RESULTS: There were 11 (47.8%) cases with positive serum ANCA in 23 anti-GBM glomerulonephritis patients. There were 4/11 MPO-ANCA (one with positive PR3-ANCA and C-ANCA, three with negative IIF-ANCA), 1/11 PR3-ANCA (with positive MPO-ANCA and C-ANCA), 3/11 P-ANCA (with negative ELISA-ANCA) and 5/11 C-ANCA (one with positive PR3-ANCA and MPO-ANCA, and the other four with negative ELISA-ANCA). No BPI-ANCA was detected. No different clinicopathologic features were found between Groups A and B. Both were different from Group C in age, sex ratio, frequence of anuria and ESRD, variety of crescents, glomerular sclerosis, vessel lesion and prognosis. CONCLUSION: Our data demonstrate that ANCA in Chinese patients with anti-GBM CGN is not rare. The major target antigen of ANCA is MPO. ANCA seems not to be correlated with disease activity.